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S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy

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ClinicalTrials.gov Identifier: NCT00134056
Recruitment Status : Completed
First Posted : August 24, 2005
Results First Posted : May 2, 2017
Last Update Posted : October 27, 2021
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
SWOG Cancer Research Network

Tracking Information
First Submitted Date  ICMJE August 22, 2005
First Posted Date  ICMJE August 24, 2005
Results First Submitted Date  ICMJE January 4, 2017
Results First Posted Date  ICMJE May 2, 2017
Last Update Posted Date October 27, 2021
Study Start Date  ICMJE August 2006
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
  • Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer. [ Time Frame: Up to 7 years after study opens ]
    Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact.
  • Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer. [ Time Frame: Up to 7 years after study opens ]
    Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
  • Compare Pain Progression Between the Two Study Arms. [ Time Frame: Up to 52 weeks ]
    Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization.
  • Compare Qualitative and Quantitative Toxicity Between the Two Study Arms [ Time Frame: Assessed every 3 weeks up to 52 weeks ]
    Only adverse events that are possibly, probably or definitely related to study drug are reported.
  • Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm. [ Time Frame: Up to 7 years after study opens ]
    PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression.
  • Compare Objective Responses Between the Two Treatment Groups in Patients With Measurable Disease as Defined by RECIST Criteria. [ Time Frame: Up to 52 weeks ]
    Complete Response (CR): Complete disappearance of all measurable and non-measurable disease. No new lesions. No disease related symptoms. Normalization of markers and other abnormal lab values. PSA ≤ .2 ng/ml. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 4, 2017)
  • Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI) [ Time Frame: up to 18 months study period ]
    Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of "0" will be defined as "stable" if their WPS remains "0" for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment
  • Number of Patients With a Change in Functional Status [ Time Frame: up to 18 months study period ]
    Functional status will be measured with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index. The FACT-P also addresses four general domains of QOL (physical, functional, emotional, and social well-being subscales) as well as symptom concerns associated with prostate cancer and its treatment.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE S0421, Docetaxel and Prednisone With or Without Atrasentan in Treating Patients With Stage IV Prostate Cancer and Bone Metastases That Did Not Respond to Previous Hormone Therapy
Official Title  ICMJE Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer
Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, prednisone, and atrasentan work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. It is not yet known whether docetaxel, prednisone, and atrasentan are more effective than docetaxel and prednisone in treating prostate cancer.

PURPOSE: This randomized phase III trial is studying docetaxel, prednisone, and atrasentan to see how well they work compared to docetaxel and prednisone in treating patients with stage IV prostate cancer and bone metastases that did not respond to previous hormone therapy.
Detailed Description

OBJECTIVES:

Primary

  • Compare the survival and progression-free survival of patients with hormone-refractory stage IV prostate cancer and bone metastases treated with docetaxel and prednisone combined with either atrasentan vs placebo.

Secondary

  • Compare pain progression of patients treated with these regimens.
  • Compare the qualitative and quantitative toxicity of these regimens in these patients.
  • Compare the quality of life, in terms of palliation of metastatic bone pain and improvement in functional status, of patients treated with these regimens.
  • Compare prostate-specific antigen (PSA) response rates in patients treated with these regimens.
  • Compare objective response in patients with measurable disease treated with these regimens.
  • Determine whether a 30% reduction in PSA and the slope of PSA from baseline to 3 months is a surrogate marker for survival in patients treated with these regimens.
  • Correlate PSA progression with clinical progression and death in patients treated with these regimens.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to disease progression (measurable or non-measurable disease progression vs prostate-specific antigen progression only), use of bisphosphonates at study entry (yes vs no), worst pain, measured by the Brief Pain Inventory "pain" scale (< grade 4 vs ≥ grade 4), and extraskeletal metastases (yes vs no). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks in the absence of disease progression* or unacceptable toxicity.
  • Arm II: Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks in the absence of disease progression* or unacceptable toxicity.

NOTE: *Patients with PSA progression alone will be allowed to continue treatment

Quality of life is assessed at baseline, before courses 4, 7, and 10, and then after completion of study treatment.

After completion of study treatment, patients are followed every 3 months for 1 year and then every 6 months for up to 3 years from study entry.

PROJECTED ACCRUAL: A total of 930 patients will be accrued for this study within 4 years.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Metastatic Cancer
  • Prostate Cancer
Intervention  ICMJE
  • Drug: atrasentan hydrochloride
    Given orally
    Other Name: atrasentan
  • Drug: docetaxel
    Docetaxel given IV and prednisone given orally
    Other Name: taxotere
  • Drug: prednisone
    Docetaxel given IV and prednisone given orally
    Other Name: steroid
  • Other: placebo
    Given orally
Study Arms  ICMJE
  • Active Comparator: Arm I: placebo
    Patients receive docetaxel and prednisone as in arm I. Patients also receive oral placebo once daily on days 1-21. Treatment repeat every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral placebo treatment for up to 52 weeks.
    Interventions:
    • Drug: docetaxel
    • Drug: prednisone
    • Other: placebo
  • Experimental: Arm II: atrasentan hydrochloride
    Patients receive docetaxel IV over 1 hour on day 1. Patients also receive oral atrasentan and oral prednisone once daily on days 1-21. Treatment repeats every 21 days for up to 12 courses. Patients with stable or responding disease after course 12 may register for continued oral atrasentan treatment for up to 52 weeks.
    Interventions:
    • Drug: atrasentan hydrochloride
    • Drug: docetaxel
    • Drug: prednisone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: February 24, 2014)		 1038
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE February 2016
Actual Primary Completion Date February 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed adenocarcinoma of the prostate

    • Stage IV disease (any T, any N, M1b)

      • Evidence of bone metastases by bone scan or MRI

  • Measurable or nonmeasurable disease

    • Soft tissue disease that has been irradiated within the past 2 months is not assessable as measurable disease

  • Hormone-refractory disease despite androgen deprivation and antiandrogen withdrawal, as defined by 1 of the following criteria:

    • Prostate-specific antigen (PSA) progression, defined as 3 consecutive rising PSA levels* taken ≥ 1 week apart

      • PSA ≥ 5 ng/mL NOTE: *If the third confirmatory PSA level is < the second level, the patient is considered eligible provided a fourth PSA level is > the second level
    • Progression of measurable disease
    • Progression of nonmeasurable disease by bone scan

  • Must have undergone surgical or medical (e.g., luteinizing hormone-releasing hormone [LHRH] agonist [e.g., leuprolide or goserelin] or LHRH antagonist therapy) castration

    • Patients who have undergone medical castration must continue LHRH agonist or antagonist therapy during study treatment
  • Must have completed 12 courses of blinding protocol treatment (atrasentan/placebo) AND stopped docetaxel for any reason (including completion of 12 courses) other than progressive disease
  • No symptomatic pleural effusion
  • No third space fluid accumulation (e.g., ascites)

  • No prior or concurrent brain metastases

    • Patients with clinical evidence of brain metastases must have a negative brain CT scan or MRI within the past 8 weeks

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • Zubrod 0-3* NOTE: For a performance status of 3, the cause must be due to pain secondary to bone metastases

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Other

  • Fertile patients must use effective contraception
  • Able to take oral medication without crushing, dissolving, or chewing tablets
  • No major infection
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage I or II cancer in complete remission
  • No symptomatic sensory neuropathy ≥ grade 2
  • No history of hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80
  • No other significant, active medical illness that would preclude study treatment or survival

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No more than 1 prior systemic vaccine or biologic therapy

    • At least 4 weeks since prior vaccine or biologic therapy and recovered
  • No concurrent biological response modifiers
  • No concurrent prophylactic colony-stimulating factors

Chemotherapy

  • More than 2 years since prior adjuvant therapy with a single non-taxane-containing cytotoxic regimen
  • No prior cytotoxic chemotherapy for metastatic prostate cancer
  • No other concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 6 weeks since prior bicalutamide or nilutamide AND has subsequent disease progression
  • At least 4 weeks since prior flutamide or ketoconazole AND has subsequent disease progression
  • Prior or concurrent megestrol for treatment of hot flashes allowed
  • No other concurrent corticosteroid or hormonal therapy unless continuing luteinizing hormone-releasing hormone treatment and/or bisphosphonate therapy

Radiotherapy

  • See Disease Characteristics
  • Prior samarium allowed
  • At least 3 weeks since prior radiotherapy and recovered
  • No prior radiotherapy to ≥ 30% of the bone marrow
  • No prior strontium
  • No concurrent radiotherapy

Surgery

  • See Disease Characteristics
  • At least 3 weeks since prior surgery and recovered

Other

  • More than 4 weeks since prior investigational drugs

  • Concurrent bisphosphonates allowed provided therapy is started prior to study entry, dose is maintained during the first 12 weeks of study treatment, and patient meets criteria for disease progression

    • No initiation of bisphosphonates during the first 12 weeks of study treatment

  • No concurrent herbal medications or food supplements (e.g., PC-SPES, saw palmetto, Hypericum perforatum [St. John's wort])

    • Concurrent daily vitamins and calcium supplements allowed

  • At least 14 days since prior and no concurrent administration of any of the following:

    • Antibiotics (e.g., clarithromycin, erythromycin, troleandomycin, rifampin, rifabutin, and rifapentine)
    • Antifungals (e.g., itraconazole, ketoconazole, fluconazole [doses > 200 mg/day], and voriconazole)
    • Antidepressants (e.g., nefazodone and fluvoxamine)
    • Calcium channel blockers (e.g., verapamil, diltiazem)
    • Miscellaneous (e.g., amiodarone [no use within 6 months prior to study entry], grapefruit juice, bitter orange, or modafinil)
    • Anticonvulsants (e.g., phenytoin, carbamazepine, phenobarbital, and oxcarbazepine)
    • Antibiotics (e.g., rifampin, rifabutin, and rifapentine)
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00134056
Other Study ID Numbers  ICMJE CDR0000439434
S0421 ( Other Identifier: SWOG )
U10CA032102 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://swog.org/Visitors/Download/Policies/Policy43.pdf
Current Responsible Party SWOG Cancer Research Network
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE SWOG Cancer Research Network
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: David I. Quinn, MD University of Southern California
Study Chair: Maha Hadi A. Hussain, MD University of Michigan Rogel Cancer Center
Study Chair: Primo N. Lara, MD University of California, Davis
Study Chair: Mark Garzotto, MD Portland VA Medical Center
PRS Account SWOG Cancer Research Network
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP